1-Boc-piperazine

In the present study, a practical method to prepare piperazinyl amides of 18β-glycyrrhetinic acid was developed. Two main procedures for the construction of important intermediate 8 are discussed. One procedure involves the amidation of 1-Boc-piperazine with 3-acetyl-18β-glycyrrhetinic acid, prepared by the reaction of 18β-glycyrrhetinic acid with acetic anhydride without any solvent at 130 °C. The other procedure to prepare compound 8 involves the amidation of 18β-glycyrrhetinic acid followed by the esterification with acetic anhydride. Finally, compound 8 underwent N-Boc deprotection to prepare product 4. To ascertain the scope of the reaction, another C-3 ester derivative 17 was tested under the optimized reaction conditions. Furthermore, the reasons for the appearance of byproducts were elucidated. Crystallographic data of a selected piperazinyl amide is reported.

Introduction: Recent advances in the field of poly (2-oxazolines) as bio-inspired synthetic pseudopeptides have proven their potential biomedical applications such as drug delivery and tissue engineering. Methods: In order to fabricate a biodegradable micellar nanoparticle of poly (2-ethyl 2-oxazoline)-b-poly (benzyl L-glutamate) or pEOx-b-pBLG, "grafting-from" synthesis approach was used involving consecutive steps of cationic ring-opening polymerization of 2-ethyl-2-oxazoline, amine functionalization of pEOx using 1-Boc-piperazine and N-carboxyanhydride polymerization of γ-benzyl- L-glutamate. Following hydrolysis of the copolymer, the protecting γ-benzyl groups were removed yielding a double-hydrophilic block ionomer of pEOx-b-poly (L-glutamic acid). The polymers were characterized by FTIR, 1H-NMR, size exclusion chromatography and differential scanning calorimetry (DSC). Aqueous assembly of the polymers was investigated by pyrene assay, dynamic light scattering, and transmission electron microscopy. MTT cytotoxicity assay was also performed to determine the cytocompatibility in various tumor cell lines. Results: The polymeric micelles presented a uni-modal size distribution with mean hydrodynamic diameter of 149.8 ± 10.6 nm and critical aggregation concentration of 60 µg/mL. The average molecular weight of pEOx increased from ~ 14 to 20 kDa for pEOx-b-poly (L-glutamic acid) as determined by light scattering (Debye plot), indicating a successful copolymerization. MTT assay showed little to no practical cytotoxicity at concentrations below 1 mg/mL. Conclusion: Multi-step synthesis of pEOx-b-pBLG and subsequent alkaline hydrolysis were performed to obtain the block ionomer pEOx-b-poly (L-glutamic acid). Both pEOx-based copolymers can be considered for various potential applications such as loading and delivery of drugs, genes, and contrast agents either by chemical conjugation or physical loading.

A series of new 5-piperidinyl and 5-piperazinyl-1H-benzo[d]imidazol-2(3H)-ones have been synthesized and evaluated for dual D2 and 5-HT1A receptor binding affinities. The synthesized ligands are structurally related to bifeprunox, a potential atypical antipsychotic, having potent D2 receptor antagonist and 5-HT1A receptor agonist properties. The Suzuki-Miyaura reaction of cyclic vinyl boronate with appropriate aryl halide yielded arylpiperidine, which was eventually transformed to piperidinyl-1H-benzo[d]imidazol-2(3H)-one. The reductive amination of the latter with appropriate biarylaldehdyes rendered the synthesis of 5-piperidinyl-1H-benzo[d]imidazol-2(3H)-ones. Likewise, the Buchwald-Hartwig coupling reactions of 1-boc-piperazine with appropriate aryl halide and subsequent removal of the boc group rendered arylpiperazine. The reductive amination of the latter with appropriate biarylaldehdyes accomplished the synthesis of 5-piperazinyl-1H-benzo[d]imidazol-2(3H)-ones. The structure-activity relationship studies showed that cyclopentenylpyridine and cyclopentenylbenzyl groups contribute significantly to the dual D2 and 5-HT1A receptor binding affinities of these compounds.